Jordovic Jelena, Bojovic Ksenija, Simonovic-Babic Jasmina, Gasic Vladimir, Kotur Nikola, Zukic Branka, Vukovic Marija, Pavlovic Sonja, Lazarevic Ivana, Bekic Ivana, Nikolic Natasa, Uroševic Aleksandar, Mitrovic Nikola, Delic Dragan
Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia, Belgrade, Serbia.
Medical Faculty, University of Belgrade, Belgrade, Serbia.
J Med Biochem. 2019 Mar 1;38(1):45-52. doi: 10.2478/jomb-2018-0015. eCollection 2019 Mar.
Chronic hepatitis C (CHC) is a significant cause of liver related morbidity and mortality worldwide. The role of genetics in the host response to hepatitis C virus is not elucidated. Genetic variations in gene are the most common cause of hereditary unconjugated hyperbilirubinemia-Gilbert syndrome. This is the first study investigating the association of TA repeats promoter genotypes with the degree of liver injury, viremia and biochemical markers in CHC patients with advanced liver injury and late virological relapse.
Genetic testing of TA repeats promoter genotypes was performed in 42 CHC patients with advanced fibrosis and cirrhosis who achieved sustained virological response and 42 healthy blood donors. CHC patients were evaluated for clinical findings, laboratory tests and imaging.
*28 genotype (7/7 TA repeats) was observed in 23.8% CHC patients and 16.7% healthy controls with no significant difference in genotype frequencies (p=0.49). Pretreatment levels of ferritin and bilirubin were associated with the presence of genotype, indicating its potential as a predictive marker. However, in our study, there was no correlation of genotype with the degree of fibrosis or viremia. During antiviral treatment, dose reductions and treatment interruptions, as well as treatment success and occurrence of late virological relapse were not related to the presence of genotype in CHC patients with severe liver injury.
Frequencies of genotype are high in both Serbian CHC patients and healthy subjects. The presence of genotype was not associated with ribavirin-related adverse effects and had no effect on long term outcome in CHC patients.
慢性丙型肝炎（CHC）是全球肝脏相关发病率和死亡率的重要原因。遗传学在宿主对丙型肝炎病毒反应中的作用尚未阐明。基因中的遗传变异是遗传性非结合性高胆红素血症——吉尔伯特综合征最常见的原因。这是第一项研究TA重复序列启动子基因型与晚期肝损伤和病毒学复发延迟的CHC患者肝损伤程度、病毒血症及生化标志物之间关联的研究。
对42例实现持续病毒学应答的晚期纤维化和肝硬化CHC患者及42名健康献血者进行TA重复序列启动子基因型的基因检测。对CHC患者进行临床检查、实验室检测和影像学评估。
23.8%的CHC患者和16.7%的健康对照者中观察到*28基因型（7/7 TA重复序列），基因型频率无显著差异（p = 0.49）。铁蛋白和胆红素的治疗前水平与该基因型的存在相关，表明其作为预测标志物的潜力。然而，在我们的研究中，该基因型与纤维化程度或病毒血症无相关性。在抗病毒治疗期间，剂量减少和治疗中断，以及治疗成功和晚期病毒学复发的发生与严重肝损伤的CHC患者中该基因型的存在无关。
塞尔维亚CHC患者和健康受试者中*28基因型的频率都很高。*28基因型的存在与利巴韦林相关的不良反应无关，对CHC患者的长期预后也无影响。
